Bacteria-Induced Colloidal Encapsulation for Probiotic Oral Delivery

Abstract

Probiotic oral delivery has crucial implications in biomedical engineering, but its oral bioavailability remains unsatisfactory because of the limited survival and colonization of probiotics in the harsh gastrointestinal tract. Here, a bacteria-induced encapsulation strategy is achieved by assembling metastable colloids to enhance the oral bioavailability of probiotics. The colloids (NTc) composed of amino-modified poly-β-cyclodextrin and tannic acid are formed based on the balance of host-guest interaction-driven attraction and electrostatic repulsion between colloids. Negatively charged probiotics electrostatically attract positively charged NTc to break the balance and induce further assembly surrounding the probiotics. Through a facile one-step mixing, 97% of bacteria are rapidly encapsulated into NTc shells within 10 s, with a high utilization rate of feeding colloids of 91%. More importantly, we show that the compact, thick, and positively charged NTc shells synergistically endow the encapsulated probiotics with strong resistance against simulated gastric fluid with an excellent survival rate of up to 19%, 7500 times superior to the commercial enteric material L100. Moreover, owing to the dynamically noncovalent and self-adaptive nature of host-guest interactions, NTc shells support the proliferation of the encapsulated EcN comparable with that of the naked EcN. In vitro and in vivo experiments also confirm that the NTc-encapsulated probiotics possess durable intestinal adhesion, continuous proliferation activity, enhanced oral bioavailability, good oral biosafety, and excellent therapeutic efficacy in a colitis mouse model. This facile bacteria-induced colloidal encapsulation strategy may extend to various microbes as oral bioagents for treating various diseases.